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https://www.readbyqxmd.com/read/28634045/egfr-egfrviii-remodels-the-cytoskeleton-via-epigenetic-silencing-of-ajap1-in-glioma-cells
#1
Chao Yang, Yan-Sheng Li, Qi-Xue Wang, Kai Huang, Jian-Wei Wei, Yun-Fei Wang, Jun-Hu Zhou, Kai-Kai Yi, Kai-Liang Zhang, Bing-Cong Zhou, Cong Liu, Liang Zeng, Chun-Sheng Kang
EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28631186/association-between-epidermal-growth-factor-receptor-amplification-and-adp-ribosylation-factor-1-methylation-in-human-glioblastoma
#2
Concha López-Ginés, Lara Navarro, Lisandra Muñoz-Hidalgo, Enrique Buso, José Manuel Morales, Rosario Gil-Benso, Mariela Gregori-Romero, Javier Megías, Pedro Roldán, Remedios Segura-Sabater, José Manuel Almerich-Silla, Daniel Monleón, Miguel Cerdá-Nicolás
PURPOSE: Glioblastoma (GB) is the most frequent and most malignant primary brain tumor in adults. Previously, it has been found that both genetic and epigenetic factors may play critical roles in its etiology and prognosis. In addition, it has been found that the epidermal growth factor receptor gene (EGFR) is frequently over-expressed and amplified in primary GBs. Here, we assessed the promoter methylation status of 10 genes relevant to GB and explored associations between these findings and the EGFR gene amplification status...
June 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28629170/egfr-and-egfrviii-promote-angiogenesis-and-cell-invasion-in-glioblastoma-combination-therapies-for-an-effective-treatment
#3
REVIEW
Stefanie Keller, Mirko H H Schmidt
Epidermal growth factor receptor (EGFR) and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM), the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their upregulation correlates with the poor prognosis of glioma patients. Glioma cell invasion and increased angiogenesis share mechanisms of the degradation of the extracellular matrix (ECM) through upregulation of ECM-degrading proteases as well as the activation of aberrant signaling pathways...
June 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28620782/role-of-key-genetic-mutations-on-increasing-migration-of-brain-cancer-cells-through-confinement
#4
Loan Bui, Sayem H Bhuiyan, Alissa Hendrick, Cheng-Jen Chuong, Young-Tae Kim
Uncontrolled invasive cancer cell migration is among the major challenges for the treatment and management of brain cancer. Although the genetic profiles of brain cancer cells have been well characterized, the relationship between the genetic mutations and the cells' mobility has not been clearly understood. In this study, using microfluidic devices that provide a wide range of physical confinements from 20 × 5 μm(2) to 3 × 5 μm(2) in cross sections, we studied the effect of physical confinement on the migratory capacity of cell lines with different types of mutations...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28604685/a-tnf-jnk-axl-erk-signaling-axis-mediates-primary-resistance-to-egfr-inhibition-in-glioblastoma
#5
Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK)...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28596941/highly-specific-and-effective-targeting-of-egfrviii-positive-tumors-with-tandab-antibodies
#6
Kristina Ellwanger, Uwe Reusch, Ivica Fucek, Stefan Knackmuss, Michael Weichel, Thorsten Gantke, Vera Molkenthin, Eugene A Zhukovsky, Michael Tesar, Martin Treder
To harness the cytotoxic capacity of immune cells for the treatment of solid tumors, we developed tetravalent, bispecific tandem diabody (TandAb) antibodies that recognize EGFRvIII, the deletion variant III of the epidermal growth factor receptor (EGFR), and CD3 on T-cells, thereby directing immune cells to eliminate EGFRvIII-positive tumor cells. Using phage display, we identified scFv antibodies selectively binding to EGFRvIII. These highly EGFRvIII-specific, fully human scFv were substantially improved by affinity maturation, achieving KDs in the picomolar range, and were used to construct a set of bispecific EGFRvIII-targeting TandAbs with a broad range of binding and cytotoxic properties...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28583430/the-egfr-variant-iii-mutant-as-a-target-for-immunotherapy-of-glioblastoma-multiforme
#7
REVIEW
Dimitry A Chistiakov, Ivan V Chekhonin, Vladimir P Chekhonin
In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand...
June 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28579776/aptamer-conjugated-pegylated-quantum-dots-targeting-epidermal-growth-factor-receptor-variant-iii-for-fluorescence-imaging-of-glioma
#8
Jiaze Tang, Ning Huang, Xiang Zhang, Tao Zhou, Ying Tan, Jiangli Pi, Li Pi, Si Cheng, Huzhi Zheng, Yuan Cheng
The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28575464/phase-ii-trial-of-dacomitinib-a-pan-her-human-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-recurrent-glioblastoma-patients-with-egfr-amplification
#9
Juan Manuel Sepúlveda-Sánchez, María Ángeles Vaz, Carmen Balañá, Miguel Gil-Gil, Gaspar Reynés, Óscar Gallego, María Martínez-García, Elena Vicente, María Quindós, Raquel Luque, Ana Ramos, Yolanda Ruano, Pedro Pérez-Segura, Manuel Benavides, Pilar Sánchez-Gómez, Aurelio Hernández-Laín
Background.: We conducted a multicenter, 2-stage, open-label, phase II trial to assess the efficacy and safety of dacomitinib in adult patients with recurrent glioblastoma (GB) and epidermal growth factor receptor (EGFR) gene amplification with or without EGFRvIII deletion. Methods.: Patients with first recurrence were enrolled in two cohorts: Cohort A) patients with EGFR gene amplification without EGFRvIII mutation; Cohort B) patients with EGFR gene amplification and EGFRvIII mutation...
June 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28574310/exosomes-as-a-biomarker-platform-for-detecting-epidermal-growth-factor-receptor-positive-high-grade-gliomas
#10
Sasidhar Venkata Manda, Yogesh Kataria, Babul Reddy Tatireddy, Balasubramaniam Ramakrishnan, Boola Gnana Ratnam, Rahul Lath, Alok Ranjan, Amitava Ray
OBJECTIVE High-grade glial brain tumors are often characterized by an elevated expression of the tumorigenic epidermal growth factor receptor variant III ( EGFRvIII). The authors sought to establish a clinically adaptive protocol as a noninvasive diagnostic tool for EGFRvIII detection through serum exosomes. METHODS Purity of serum exosome/RNA was confirmed by electron microscopy and flow cytometry and through an RNA bioanalyzer profile. EGFRvIII amplification was initially established by semiquantitative polymerase chain reaction in tumor tissues and exosomes...
June 2, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28569328/an-egfrviii-targeted-dual-modal-gold-nanoprobe-for-imaging-guided-brain-tumor-surgery
#11
Qi Yue, Xihui Gao, Yang Yu, Yang Li, Wei Hua, Kun Fan, Ren Zhang, Jun Qian, Liang Chen, Cong Li, Ying Mao
Surgery is a mainstay to treat malignant brain tumors. However, due to the infiltrative nature of these tumors, it is a great challenge for surgeons to accurately identify and excise all the tumor foci. EGFRvIII, a variant of epidermal growth factor receptor (EGFR), is found in 20% of glioblastoma cases, which is the brain tumor with the highest malignancy. In this study, we developed an EGFRvIII-targeted nanoprobe to guide glioblastoma surgery by pre-operatively defining the tumor boundary via magnetic resonance imaging (MRI) and intra-operatively guiding resection by surface-enhanced resonance Raman scattering (SERRS) imaging...
June 1, 2017: Nanoscale
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#12
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28544767/a-poly-propyleneimine-dendrimer-based-polyplex-system-for-single-chain-antibody-mediated-targeted-delivery-and-cellular-uptake-of-sirna
#13
Stefanie Tietze, Isabell Schau, Susanne Michen, Franka Ennen, Andreas Janke, Gabriele Schackert, Achim Aigner, Dietmar Appelhans, Achim Temme
Therapeutics based on small interfering RNAs (siRNAs) offer a great potential to treat so far incurable diseases or metastatic cancer. However, the broad application of siRNAs using various nonviral carrier systems is hampered by unspecific toxic side effects, poor pharmacokinetics due to unwanted delivery of siRNA-loaded nanoparticles into nontarget organs, or rapid renal excretion. In order to overcome these obstacles, several targeting strategies using chemically linked antibodies and ligands have emerged...
May 22, 2017: Small
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#14
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28500562/epithelial-growth-factor-receptor-expression-influences-5-ala-induced-glioblastoma-fluorescence
#15
Andrea O Fontana, Deborah Piffaretti, Francesco Marchi, Floriana Burgio, Ana Bela Faia-Torres, Paolo Paganetti, Sandra Pinton, Uwe Pieles, Michael Reinert
The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in high-grade glioma and glioblastoma surgery. Yet the intensity of the 5-ALA induced fluorescence may vary within the tumor. We aimed to correlate 5-ALA induced fluorescence with the expression of epithelial growth factor receptor (EGFR) and its constitutively active version EGFRvIII in different glioblastoma (GBM) cell lines. To elucidate the role of EGFR in the metabolism of 5-ALA in GBM cell lines with variable EGFR expression status, we analyzed the activation of EGFR by its primary ligand EGF, and its downstream effect on Heme oxygenase-1 (HO-1), a key enzyme regulating the metabolism of Protoporphyrin IX (PpIX), the fluorescent metabolite of 5-ALA...
May 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28487380/egfr-signals-through-a-dock180-mlk3-axis-to-drive-glioblastoma-cell-invasion
#16
Sean A Misek, Jian Chen, Laura Schroeder, Chotirat Rattanasinchai, Ashley Sample, Jann N Sarkaria, Kathleen A Gallo
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM. A majority of GBM tumors have dysregulated EGFR signaling, due most frequently to EGFR amplification or the presence of a constitutively active EGFRvIII mutant. Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that can activate multiple MAPK pathways...
May 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28453784/detection-of-wtegfr-amplification-and-egfrviii-mutation-in-csf-derived-extracellular-vesicles-of-glioblastoma-patients
#17
Javier M Figueroa, Johan Skog, Johnny Akers, Hongying Li, Ricardo Komotar, Randy Jensen, Florian Ringel, Isaac Yang, Steven Kalkanis, Reid Thompson, Lori LoGuidice, Emily Berghoff, Andrew Parsa, Linda Liau, William Curry, Daniel Cahill, Chetan Bettegowda, Frederick F Lang, E Antonio Chiocca, John Henson, Ryan Kim, Xandra Breakefield, Clark Chen, Karen Messer, Fred Hochberg, Bob S Carter
Background: RNA within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer, and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients, for the presence of tumor-associated amplifications and mutations in the epidermal growth factor receptor (EGFR). Methods: CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs...
April 27, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28428190/in-vivo-detection-of-egfrviii-in-glioblastoma-via-perfusion-magnetic-resonance-imaging-signature-consistent-with-deep-peritumoral-infiltration-the-%C3%AF-index
#18
Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M O'Rourke, Christos Davatzikos
<br />The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma non-invasively, using routine clinically-acquired imaging...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28427242/epidermal-growth-factor-receptor-variant-iii-in-head-and-neck-squamous-cell-carcinoma-is-not-relevant-for-targeted-therapy-and-irradiation
#19
Dominik Thomas Koch, Anja Pickhard, Lena Gebel, Anna Maria S Buchberger, Murat Bas, Carolin Mogler, Rudolf Reiter, Guido Piontek, Markus Wirth
BACKGROUND: The epidermal growth factor receptor (EGFR) is an important regulator of cell growth and survival, and is highly variable in tumor cells. The most prevalent variation of the EGFR extracellular domain is the EGFR variant III (EGFRvIII). Some studies imply that EGFRvIII may be responsible for the poor response to the monoclonal EGFR-antibody Cetuximab, used therapeutically in head and neck squamous cell carcinoma (HNSCC). Due to inconsistent data in the literature regarding EGFRvIII prevalence and clinical relevance in HNSCC, especially its predictive value, we examined EGFRvIII-transfected cell lines and patient tissue samples...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412740/combination-epidermal-growth-factor-receptor-variant-iii-peptide-pulsed-dendritic-cell-vaccine-with-mir-326-results-in-enhanced-killing-on-egfrviii-positive-cells
#20
Jianlong Li, Feng Wang, Guangzhi Wang, Ying Sun, Jinquan Cai, Xing Liu, Junhe Zhang, Xiaoyan Lu, Yongli Li, Meng Chen, Lingchao Chen, Chuanlu Jiang
The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells...
April 18, 2017: Oncotarget
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